PXD028125

PXD028125 is an original dataset announced via ProteomeXchange.

Title	A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells
Description	Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs potentially regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent and selective inhibitors of key ALDHs may represent a novel CSC-directed treatment paradigm for ALDH+ cancer types. Of the many ALDH isoforms, we and others have implicated the elevated expression of ALDH1A3 in mesenchymal glioma stem cells (MES GSCs) as a target for the development of novel therapeutics. To this end, we used our structure of human ALDH1A3 combined with in silico modeling to identify a selective, active-site inhibitor of ALDH1A3. The lead compound, MCI-INI-3, is a selective competitive inhibitor of human ALDH1A3 and shows poor inhibitory effect on the structurally related isoform ALDH1A1. Mass spectrometry-based cellular thermal shift analysis revealed that ALDH1A3 is the primary binding protein for MCI-INI-3 in MES GSC lysates. The inhibitory effect of MCI-INI-3 on retinoic acid biosynthesis is comparable with that of ALDH1A3 knockout, suggesting that effective inhibition of ALDH1A3 is achieved with MCI-INI-3. Further development is warranted to characterize the role of ALDH1A3 and retinoic acid biosynthesis in glioma stem cell growth and differentiation.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_09:29:56.461.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Mullett
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-25 04:27:41	ID requested
⏵ 1	2022-02-15 09:29:57	announced

Li J, Garavaglia S, Ye Z, Moretti A, Belyaeva OV, Beiser A, Ibrahim M, Wilk A, McClellan S, Klyuyeva AV, Goggans KR, Kedishvili NY, Salter EA, Wierzbicki A, Migaud ME, Mullett SJ, Yates NA, Camacho CJ, Rizzi M, Sobol RW, A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells. Commun Biol, 4(1):1420(2021) [pubmed]

ProteomeXchange project tag: Cancer (B/D-HPP), Human Proteome Project

submitter keyword: Human, cancer, Target-ID, small molecule

Nathan A. Yates
contact affiliation	Scientific Director Biomedical Mass Spectrometry Center University of Pittsburgh
contact email	yatesn@pitt.edu
lab head
Steven Mullett
contact affiliation	Technical Director Health Sciences Metabolomics and Lipidomics Core Pharmacology and Chemical Biology University Of Pittsburgh
contact email	sjmst52@pitt.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD028125

PRIDE project URI

• PRIDE
  1. PXD028125
     1. Label: PRIDE project
     2. Name: A specific inhibitor of ALDH1A3 regulates retinoic acid biosynthesis in glioma stem cells